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Mismatch-Repair
(MMR) Responses to DNA Lesions
September
9-10 , 2005
Oregon Health & Science University • Portland,
Oregon
Oregon State University • Corvallis, Oregon
When
DNA damage temporarily overwhelms mammalian lesion-removal
systems, error-prone replication past unrepaired
lesions can generate mutations, cell-cycle arrest
can provide more time to remove lesions, and programmed
death (apoptosis) can eliminate hopelessly damaged
cells. Mismatch-repair (MMR) systems frequently
suppress mutations generated by bypass polymerases
and help signal to checkpoint and apoptosis pathways.
Thus, the cancer predisposition of human beings
with defective MMR genes may reflect deficiencies
in some or all of these responses to DNA damage,
as well as increased spontaneous mutation due
to impaired correction of replication errors (base-mismatches).
Also, the efficacy of certain anti-tumour drugs
depends on MMR-mediated apoptosis. This mini-conference
focuses on both mechanistic and clinical aspects
of MMR responses to DNA damage, at biochemical,
cellular-signaling, and mutagenesis/carcinogenesis
levels. The DNA lesions are induced by sunlight
(UV photoproducts), endogenous oxygen metabolism
(8-oxoguanine and other oxidized purines), cooked-meat
heterocyclic amines, and anti-cancer and immunosuppressant
drugs (O6-methylguanine, G[cisplatin]G crosslinks),
or ionizing radiation (DNA breaks).
For
early arrivers on Friday, we offer user-friendly
downtown Portland. For free time on Saturday,
a tour of the scenic Williamette Valley, including
a few of its wineries, or activities at and around
OSU.
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